Exercise training is an effective modality for prevention of cardiovascular disease, diabetes mellitus and for improvements in other cardiovascular risk factors. Despite some recent advances in the field, many questions remain about the effects of mode, amount and intensity of exercise training on cardiovascular risk in humans. This proposal represents a competitive renewal for our project Peripheral Effects of Exercise on Cardiovascular Health (HL57354). During the past funding period our goal was to investigate the influence of aerobic exercise training dose and intensity on metabolic parameters of cardiovascular health, specifically glucose and lipid metabolism, with the underlying mechanistic hypothesis that most of the beneficial effects would be mediated through changes in intrinsic skeletal muscle characteristics, such as capillarity, oxidative and glycolytic metabolism and molecular mediators of lipid and glucose metabolism in skeletal muscle. In initial findings from these studies, we observed that aerobic exercise training has pleiomorphic effects on glucose and lipid markers of cardiovascular risk and body habitus, and we have begun to sort out the mechanistic relationships between aerobic exercise training amount and intensity on whole body glucose and lipid metabolism. In this competitive renewal, we propose to extent our work to the determine the effects and mechanisms of resistance training as well, by investigating whether resistance training alone or in combination with aerobic training has effects similar to aerobic training on metabolic markers ol cardiovascular risk. We hypothesize that it does, but that the mechanisms are different between the two modalities and should be therefore complementary and additive in effecting glucose and lipid metabolism in individuals at risk for cardiovascular disease. Mechanistic models will incorporate studies of body habitus and skeletal muscle. The work will encompass the following Specific Aims: 1) To determine whether resistance training alone or in combination with aerobic training improves lipoprotein and glucose metabolism. A secondary aim will determine the gender-specific component of the effects. 2) To determine what component of these responses are mediated through skeletal muscle and body habitus adaptations. 3) To determine the time-dependent component of moderate amount aerobic training. 4) To explore age and gender dependencies of the responses. We believe that these studies are a natural extension of our previous work and likewise should have a major impact on the design of exercise training regimens and advice for those al risk for cardiovascular disease and help to define the mechanisms that underlie exercise benefits.